Impact of rotavirus vaccination on seizure hospitalizations in children: A systematic review

Background: Previous studies found conflicting results about the effect of rotavirus (RV) vaccination on seizure hospitalizations in children younger than 5 years old. Objectives: To evaluate the evidence of the impact of RV vaccination on the prevention of seizure hospitalizations in children. Methods: A systematic review was conducted in the electronic database MEDLINE of all observational studies in children younger than 5 years old published since 2006. Two reviewers performed title/abstract, full-text review, and data extraction. Results: Thirteen studies met eligibility criteria. Nine studies reported a significant reduction in seizure hospitalizations upon RV vaccine introduction, three studies reported an absence of significant impact, and one study reported a significant rise in seizure hospitalization after the introduction of RV vaccines. Limitations: The great variability between study designs, case definitions and potential biases prevent quantifying the impact of RV vaccination against seizure hospitalizations. Conclusions: RV vaccination might prevent seizure hospitalizations in children; however, robust, and well-designed studies are needed to better determine the strength of this associationMedicin

Herpes zoster risk and burden of disease in immunocompromised populations: a population-based study using health system integrated databases, 2009–2014

Background: Estimate the incidence of herpes zoster (HZ), its complications and healthcare utilization rates in adults (≥ 18-years-old) with a wide range of immunocompromised (IC) conditions compared to IC-free cohort. Method: A population-based retrospective study using the Valencia healthcare Integrated Databases (VID) (2009– 2014). HZ and IC were defined using ICD-9 codes in primary care (PC) and hospitalization registers. Incidence rates (IR), risk of HZ, HZ-recurrence, HZ-complications and healthcare utilization rates were estimated in the IC-cohort compared to IC-free. Results: The study population consisted of 4,382,590 subjects, of which 578,873 were IC (13%). IR (in 1000 persons-year) of HZ overall, in IC and in IC-free cohort was 5.02, 9.15 and 4.65, respectively. IR of HZ increased with age in both cohorts and it was higher for all IC conditions studied, reaching up to twelvefold in subjects with stem cell transplantation. IC subjects had 51% higher risk of developing HZ, 25% higher HZrecurrence and the risk of HZ-complications was 2.37 times higher than in IC-free. HZ-related healthcare utilization was higher in the IC-cohort than in IC-free (number of hospitalizations 2.93 times greater, hospital stays 12% longer, 66% more HZ-specialist visits, 2% more PC visits, sick leaves 18% longer and 20% higher antiviral dispensation). Conclusions: Patients suffering from all the IC conditions studied are at higher risk of developing HZ, HZrecurrence and post-herpetic complications, which implies a substantial morbidity and a high consumption of resources. These results should be considered for vaccine policy implementation.Funding for this study was provided by GlaxoSmithKline Biologicals SA (GSK study identifier 207685). GlaxoSmithKline Biologicals SA was provided the opportunity to review a preliminary version of this manuscript for factual accuracy but the authors are solely responsible for final content and interpretation. The Company (GSK) had no role in the analysis or discussion of the results.Medicin

Epidemiology of schizophrenia and its management over 8-years period using real-world data in Spain

Background: Real-World Data (RWD) studies provide important insights in disease epidemiology, in real clinical populations, with long follow-up periods. The aim of the present study was to describe the epidemiology of schizophrenia spectrum disorders (SD) during an 8-year period in Spain. Methods: A retrospective cohort of subjects aged 15 to 64 years was followed-up using electronic healthcare databases of the Valencia region (2008–2015). SD cases included outpatient and inpatient settings (ICD 9 codes 295.XX). Prevalence of SD was assessed. Incidence rate (IR) in the subpopulation aged between 15 and 34 years was also provided. Healthcare utilization (HCU) rates, including outpatient, specialists, hospitalizations and antipsychotic dispensations were estimated. Results: The cohort included 3,976,071 subjects; 24,749 of them had a prevalent diagnosis of SD. The overall prevalence for SD was 6.2 per 1000 persons. SD were 76% more prevalent in men than women. IR in the subpopulation aged between 15 and 34 years was 50.25 per 100,000 persons years and was more than 2 times higher for men than for women. 83.4% of the overall outpatient visits from the cohort of patients were related to SD. The 21,095 overall hospitalizations with the SD code resulted in 286,139 days of hospitalization, with a median of 4 days (IQR: 1.6–9.2) per person-year. 93.2% of subjects diagnosed with SD were ever treated with some antipsychotic drug during the study period, and 70% of the patients were ever treated with antipsychotic polypharmacy. Conclusions: This large population-based study using RWD provides novel and recent information SD in a southern European country. The prevalence and IR of SD showed is greater than previously published and higher in men than in women. The fact of having used a large arsenal of electronic data (including outpatient and inpatient) for 8 years may have influenced. SD represents high burden and healthcare utilization. Contrary to guidelines recommendations the majority of patients were ever treated with antipsychotic polypharmacy.This study was supported by Janssen pharmaceutical. The company had no role in the analysis or discussion of the resultMedicin

Human papillomavirus vaccines effectiveness to prevent genital warts: A population-based study using health system integrated databases, 2009-2017.

Objectives: To assess the effectiveness of the HPV vaccines in preventing genital warts (GW) in women aged 14–23 years and to estimate the incidence of GW in the whole population aged from 14 to 65. Design: Population-based retrospective cohort study using real-world data from the Valencia health system Integrated Databases (VID). Study population: All subjects aged 14–65 years residing in the Valencia Region during 2009–2017 (n = 4,492,724), including a cohort of 563,240 females aged 14–23 years followed-up for the vaccine effectiveness (VE) estimations. Main outcome measures: Incident cases of GW defined as the first activation of GW-related codes (ICD-9- CM 078.11 or ICD-10-CM A63.0) in hospital, primary and specialized care during the study period. Adjusted VE was estimated as (1-Relative Risk (RR)) 100 by a negative binomial Bayesian model. Results: There were 23,049 cases of GW in the overall population and 2,565 in the females’ cohort 14– 23 years old. The incidence rate (IR) (in 100,000 persons-year) was 69.1 (95% CI 68.21–69.99) in the population overall, being higher in men (72.73; 95% CI 71.45–74.04). The IR of GW was 104.08 (95% CI 100.79–108.94) in the cohort of young women. The RR of GW increased with age from 14 to 21 years, reaching a plateau from 21 to 23. The VE of a complete schedule was 74% (95% CrI 68–79) for quadrivalent HPV vaccine (HPV4v). No effectiveness was seen with a full vaccination course with the bivalent HPV vaccine (HPV2v) in girls up to 21 years old. GW IR tends to be higher in unvaccinated cohorts covered by HPV4v vaccine than in unvaccinated cohorts not covered by HPV4v vaccine. Conclusions: A complete HPV4v vaccination schedule was 74% effective in reducing GW in our population. Our results also suggest an indirect protection to unvaccinated and HPV2v vaccinated girlsThis study has been funded by MSD. MSD had no role in the design, collection, analysis, interpretation of the data and writing of the article, and had no access to the data. MSD did not intervene in the decision to submit the manuscript for publication.Medicin

The impact of childhood RSV infection on children’s and parents’ quality of life: a prospective multicenter study in Spain

Background: Several immunisation candidates against RSV are in late-stage clinical trials. To evaluate the benefts of a potential vaccination programme, both economic and health benefts will be needed. Health benefts are usually measured in Health-related Quality of Life (HRQoL) loss using standardised questionnaires. However, there are no RSV-specifc questionnaires validated for children under 2 years, in whom most RSV episodes occur. Therefore, HRQoL estimates are taken from literature or inadequate tools. We determined HRQoL loss and direct costs due to an RSV episode in children younger than 2 years and their caregivers during a month of follow up, using a new questionnaire administered online. Methods: An observational prospective multicentre surveillance study was conducted in children aged younger than two years. Children were recruited from 8 primary care centres and 1 hospital in the Valencia region and Cata‑ lonia (Spain). RSV-positive cases were obtained by immunochromatographic test. HRQoL was assessed using a new ad-hoc 38 item-questionnaire developed. Parents of infected children completed 4 questionnaires at four timepoints (day 0, 7, 14 and 30) after diagnosis. Results: 117 children were enrolled in the study and 86 (73.5%) were RSV+. Median (interquartile range; IQR) scores were 0.52 (0.42–0.68), 0.65 (0.49–0.79), 0.82 (0.68–0.97) and 0.94 (0.81–1), for days 0, 7, 14 and 30, respectively. Compared to total recovery (Q30), HRQoL loss was 37.5%, 31.5% and 8.9% on days 0, 7 and 14 since diagnosis of the disease. The total median cost per patient (including treatments) was €598.8 (IQR: 359.63–2425.85). Conclusions: RSV had almost 40% impact on HRQoL during the frst week since onset of symptoms and the median cost per episode and patient was about €600. These results represent a substantial input for health-economic evalua‑ tions of future RSV-related interventions such as vaccination.This study was funded by Conselleria d’Educació, Cultura i Esport of The Valencia Region of Spain.Medicin

Risk and impact of herpes zoster among COPD patients: a population-based study, 2009–2014

Abstract Background The objective of this study was to assess the incidence of Herpes Zoster (HZ) among patients with chronic obstructive pulmonary disease (COPD) and the impact of HZ on the underlying COPD. Methods A retrospective cohort of all subjects older than 49 years was followed up between 2009 and 2014 using population and health databases of Valencia Region (Spain). HZ and COPD were identified using ICD-9 codes, differentiating COPD patients with inhaled corticosteroids prescriptions (COPD-ICS). The incidence of HZ was compared among 3 groups [non-COPD, COPD and COPD-ICS populations] and use of healthcare resource due to HZ for 6 months following HZ diagnosis through different statistical generalized linear models (GLM). We also compared resources consumption due to COPD before and after HZ. Results The cohort consisted of 2,289,485 subjects, including 161,317 COPD patients of which 29,708 were COPD-ICS. HZ incidence rates were 11 (95% confidence interval [CI]: 10.7–11.4) and 13 (95% CI: 12.3–13.8) cases/1000 persons-year for COPD and COPD-ICS populations respectively. Incidence increased with age in all groups. The risk of HZ rose by 45 and 61% among COPD and COPD-ICS patients respectively compared to non-COPD (95% credible intervals [CrI]: 1.41–1.5 and 1.52–1.71 respectively). COPD patients consumed more resources due to their HZ than non-COPD. There was no statistically significant impact of the HZ on the resources consumed due to COPD during the 6 months post-HZ compared to the 6 months pre-HZ. Conclusions The presence of COPD increases the risk, severity and impact of zoster episodes

A Multivariate Age-Structured Stochastic Model with Immunization Strategies to Describe Bronchiolitis Dynamics

Bronchiolitis has a high morbidity in children under 2 years old. Respiratory syncytial virus (RSV) is the most common pathogen causing the disease. At present, there is only a costly humanized monoclonal RSV-specific antibody to prevent RSV. However, different immunization strategies are being developed. Hence, evaluation and comparison of their impact is important for policymakers. The analysis of the disease with a Bayesian stochastic compartmental model provided an improved and more natural description of its dynamics. However, the consideration of different age groups is still needed, since disease transmission greatly varies with age. In this work, we propose a multivariate age-structured stochastic model to understand bronchiolitis dynamics in children younger than 2 years of age considering high-quality data from the Valencia health system integrated database. Our modeling approach combines ideas from compartmental models and Bayesian hierarchical Poisson models in a novel way. Finally, we develop an extension of the model that simulates the effect of potential newborn immunization scenarios on the burden of disease. We provide an app tool that estimates the expected reduction in bronchiolitis episodes for a range of different values of uptake and effectiveness

Long-term impact of self-financed rotavirus vaccines on rotavirus-associated hospitalizations and costs in the Valencia Region, Spain

Abstract Background Rotavirus vaccines are available in Spain from 2007. They are recommended by the Spanish Pediatric Association, but not funded by the National Health System (NHS) and its coverage rate reached 40-50%. The hospitalization rate reduction of rotavirus caused gastroenteritis (RVAGE) directly attributable to vaccination remains unclear due to the large differences described in published studies, ranging from 14 to 44.5% in children <5 years of age, even with similar vaccination coverage. These results could be partly explained by variability in hospitalization policies, different study designs and the timeframe of observation. In addition, the direct economic impact of the reduction of hospitalizations has never been estimated. Therefore, there is a need to analyze the long-term impact of rotavirus vaccines on RVAGE and all cause gastroenteritis (AGE) hospitalizations and the national health system associated costs, minimizing potential confounders or biases. Methods A population-based, ecological study using the hospital discharge registry’s Minimum Basic Data Set (MBDS) and the vaccine register (SIV) was performed, among Valencia Region’s children <5 years old, during 2002 - 2015. RVAGE and AGE hospitalization risk was analyzed by vaccine coverage and adjusted by the total hospitalization rate for all causes to avoid external biases. The impact of AGE-associated health care utilization in prevaccine (2003–2006) versus postvaccine (2008–2014) years was also assessed. Results After vaccines licensure, the incidence of RVAGE-associated hospitalizations decreased markedly. A general vaccine coverage-related reduction in RVAGE or AGE-hospitalizations risk was observed in all age groups. Compared with unvaccinated children, RVAGE hospitalization risk decreased by 67% (95% CI: 55-67), 71% (95% CI: 58-81) and 68% (95% CI: 18-92) in children 0, 1 and 4 years of age, respectively, with a vaccination coverage between 40 and 42%. Overall, the hospital related costs were reduced around EUR 6 Mill per 105 children in 7 years. Conclusions Despite the low-medium vaccine coverage, the introduction of rotavirus vaccines had a specific coverage-related response impact in the hospitalizations for RVAGE and AGE in children <5 years and their use substantially reduced hospital related costs. The model used reassures that the estimated impact is due to the vaccination and not to other external factors

Lack of impact of rotavirus vaccines on seizure-related hospitalizations in children under 5 years old in Spain

Introduction: Up to date the impact of rotavirus (RV) vaccines on seizures has been poorly evaluated, with some studies but not all, showing different degrees of protection. Objectives: To assess the impact of RV vaccines on convulsions-related hospitalizations among children under 5 years of age residing in the Region of Valencia, Spain. Methods: A population-based, ecological study using the hospital discharge record (MBDS), the population-based administrative database (SIP) and the vaccine register (SIV), among Valencia Region's children <5 years old, during 2003 – 2015. Impact of vaccination on seizures-related hospitalization rates (780.3* ICD-9-MC code) was estimated by a multivariate Bayesian mixed Poisson regression model. Results: Since RV vaccines licensure in 2007, its coverage rate increased up to around 42%. When the impact of vaccination against seizures was controlled for potential confounders in the multivariate analysis, there was a non-statistically significant protective effect. Conclusions: We could not find any impact of RV vaccine coverage on seizure-related hospitalizations in children <5 years

Letter to the editor regarding “The role of age-sex interaction in the development of post-herpetic neuralgia”

The objective of the study was to evaluate the role of age and sex and their combined effect in the development of post-herpetic neuralgia (PHN) in a large population-based study, in order to confirm the results published previously by Amicizia et al. Data were extracted from population and healthcare databases from the Valencia Region (2009–2014). Logistic regressions were implemented to estimate the effect of increasing age on the probability of developing PHN stratified by sex. From a cohort of 2,289,485 subjects ≥ 50 years, 87,086 cases of HZ were registered and 13,658 (15.7%) of them developed PHN. In our population, PHN cases were more common in women and rose with increasing age independently of the sex